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OBJECTIVE The purpose of the study is to evaluate the relationship between HbA1c and severity of coronavirus disease 2019 (COVID-19) outcomes in patients with type 2 diabetes (T2D) with acute COVID-19 infection. RESEARCH DESIGN AND METHODS We conducted a retrospective study using observational data from the National COVID Cohort Collaborative (N3C), a longitudinal, multicenter U.S. cohort of patients with COVID-19 infection. Patients were ≥18 years old with T2D and confirmed COVID-19 infection by laboratory testing or diagnosis code. The primary outcome was 30-day mortality following the date of COVID-19 diagnosis. Secondary outcomes included need for invasive ventilation or extracorporeal membrane oxygenation (ECMO), hospitalization within 7 days before or 30 days after COVID-19 diagnosis, and length of stay (LOS) for patients who were hospitalized. RESULTS The study included 39,616 patients (50.9% female, 55.4% White, 26.4% Black or African American, and 16.1% Hispanic or Latino, with mean ± SD age 62.1 ± 13.9 years and mean ± SD HbA1c 7.6% ± 2.0). There was an increasing risk of hospitalization with incrementally higher HbA1c levels, but risk of death plateaued at HbA1c >8%, and risk of invasive ventilation or ECMO plateaued >9%. There was no significant difference in LOS across HbA1c levels. CONCLUSIONS In a large, multicenter cohort of patients in the U.S. with T2D and COVID-19 infection, risk of hospitalization increased with incrementally higher HbA1c levels. Risk of death and invasive ventilation also increased but plateaued at different levels of glycemic control.

OBJECTIVE Total pancreatectomy with islet autotransplantation (TPIAT) is indicated to alleviate debilitating pancreas-related pain and mitigate diabetes in patients with acute recurrent and chronic pancreatitis when medical/endoscopic therapies fail. Our aim was to evaluate predictors of insulin requirement at 1 year following TPIAT in a cohort of children. RESEARCH DESIGN AND METHODS This was a review of 43 pediatric patients followed after TPIAT for 1 year or longer. Primary outcome was insulin use at 1 year, categorized as follows: insulin independent, low insulin requirement ( RESULTS At 1 year after TPIAT, 12 of 41 (29%) patients were insulin independent and 21 of 41 (51%) had low and 8 of 41 (20%) had high insulin requirement. Insulin-independent patients were younger than those with low and high insulin requirement (median age 8.2 vs. 14.6 vs. 13.1 years, respectively; P = 0.03). Patients with insulin independence had a higher number of transplanted islet equivalents (IEQ) per kilogram body weight (P = 0.03) and smaller body surface area (P = 0.02), compared with those with insulin dependence. Preoperative exocrine insufficiency was associated with high insulin requirement (P = 0.03). Higher peak C-peptide measured by stimulated mixed-meal tolerance testing (MMTT) at 3 and 6 months post-TPIAT was predictive of lower insulin requirement at 1 year (P = 0.006 and 0.03, respectively). CONCLUSIONS We conclude that insulin independence following pediatric TPIAT is multifactorial and associated with younger age, higher IEQ per kilogram body weight transplanted, and smaller body surface area at time of operation. Higher peak C-peptide measured by MMTT following TPIAT confers a higher likelihood of low insulin requirement.

OBJECTIVE To describe temporal trends and correlates of glycemic control in youth and young adults (YYA) with youth-onset diabetes. RESEARCH DESIGN AND METHODS The study included 6,369 participants with type 1 or type 2 diabetes from the SEARCH for Diabetes in Youth study. Participant visit data were categorized into time periods of 2002–2007, 2008–2013, and 2014–2019, diabetes durations of 1–4, 5–9, and ≥10 years, and age groups of 1–9, 10–14, 15–19, 20–24, and ≥25 years. Participants contributed one randomly selected data point to each duration and age group per time period. Multivariable regression models were used to test differences in hemoglobin A1c (HbA1c) over time by diabetes type. Models were adjusted for site, age, sex, race/ethnicity, household income, health insurance status, insulin regimen, and diabetes duration, overall and stratified for each diabetes duration and age group. RESULTS Adjusted mean HbA1c for the 2014–2019 cohort of YYA with type 1 diabetes was 8.8 ± 0.04%. YYA with type 1 diabetes in the 10–14-, 15–19-, and 20–24-year-old age groups from the 2014–2019 cohort had worse glycemic control than the 2002–2007 cohort. Race/ethnicity, household income, and treatment regimen predicted differences in glycemic control in participants with type 1 diabetes from the 2014–2019 cohort. Adjusted mean HbA1c was 8.6 ± 0.12% for 2014–2019 YYA with type 2 diabetes. Participants aged ≥25 years with type 2 diabetes had worse glycemic control relative to the 2008–2013 cohort. Only treatment regimen was associated with differences in glycemic control in participants with type 2 diabetes. CONCLUSIONS Despite advances in diabetes technologies, medications, and dissemination of more aggressive glycemic targets, many current YYA are less likely to achieve desired glycemic control relative to earlier cohorts.

OBJECTIVETo assess the prevalence of high diabetes distress and associated factors in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY2) study cohort of young adults with youth-onset type 2 diabetes.RESEARCH DESIGN AND METHODSParticipants completed the Diabetes Distress Scale (DDS) at end-of-study visits. Factors examined for association with high distress were demographic (sex, race/ethnicity, age, education, income), medical (HbA1c, BMI, complications), psychological (depressive and anxiety symptoms), and social (number in household, offspring, health care coverage, established with diabetes care provider). Univariate logistic regression identified factors associated with high distress that were controlled for in multivariate logistic regressions.RESULTSOf 438 participants, 66% were female (mean age 26.8 years, 18% non-Hispanic White, 37% non-Hispanic Black, 38% Hispanic). High distress (DDS ≥2) was reported by 105 (24%) participants. Subscales identified 40% with high regimen distress and 29.7% with high emotional burden. A greater percentage of those with high distress were female (P = 0.002), diagnosed with hypertension (P = 0.037) and retinopathy (P = 0.005), treated with insulin, had higher HbA1c, and had moderate to severe depressive and anxiety symptoms (all P < 0.001). In multivariate analyses, female sex (P < 0.001), HbA1c (P < 0.001), anxiety symptoms (P = 0.036), and lack of health care coverage (P = 0.019) were associated with high distress, after controlling for potential confounders. Moderate to severe depressive symptoms were associated with high regimen distress (P = 0.018) and emotional burden (P < 0.001); insulin treatment was associated with high emotional burden (P = 0.027).CONCLUSIONSFuture research should identify modifiable factors associated with high diabetes distress in young adults with youth-onset type 2 diabetes that may inform distress interventions with this medically vulnerable group.

OBJECTIVE To evaluate changes in the prevalence of depressive symptoms, loneliness, and insomnia among older adults with type 2 diabetes from 2016 to 2020 and to assess risk factors for these conditions including demographics, multimorbidity, BMI, treatment group, and pre-coronavirus 2019 (COVID-19) measure scores. RESEARCH DESIGN AND METHODS This was a prospective, observational study of participants from the Look AHEAD (Action for Health in Diabetes) cohort study. Data were from two assessments before COVID-19 (visit 1: April 2016–June 2018 and visit 2: February 2018–February 2020) and one assessment during COVID-19 (visit 3: July–December 2020). Surveys were administered to assess depressive symptoms, loneliness, and insomnia. RESULTS The study included 2829 adults (63.2% female, 60.6% White, mean [SD] age 75.6 [6.0] years). The prevalence of mild or greater depressive symptoms did not change significantly between the two pre-pandemic visits (P = 0.88) but increased significantly from pre- to during COVID-19 (19.3% at V2 to 30.4% at V3; P < 0.001). Higher odds of mild or greater depressive symptoms at V3 were associated with being female (adjusted odds ratio [OR] 1.4 [95% CI 1.1–1.7]), identifying as non-Hispanic White (OR 1.4 [95% CI 1.1–1.7]), having obesity (OR 1.3 [95% CI 1.0–1.5]), and reporting mild or greater depressive symptoms at V1 (OR 4.0 [95% CI 2.9–5.4]), V2 (OR 4.4 [95% CI 3.2–5.9]), or both visits (OR 13.4 [95% CI 9.7–18.4]). The prevalence of loneliness increased from 12.3% at V1 to 22.1% at V3 (P < 0.001), while the prevalence of insomnia remained stable across visits at 31.5–33.3%. CONCLUSIONS The prevalence of mild or greater depressive symptoms in older adults with diabetes was more than 1.6 times higher during COVID-19 than before the pandemic.

OBJECTIVE To investigate glucose variations associated with glycated hemoglobin (HbA1c) in insulin-treated patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Patients included in Diabetes and Lifestyle Cohort Twente (DIALECT)-2 (n = 79) were grouped into three HbA1c categories: low, intermediate, and high (≤53, 54–62, and ≥63 mmol/mol or ≤7, 7.1–7.8, and ≥7.9%, respectively). Blood glucose time in range (TIR), time below range (TBR), time above range (TAR), glucose variability parameters, day and night duration, and frequency of TBR and TAR episodes were determined by continuous glucose monitoring (CGM) using the FreeStyle Libre sensor and compared between HbA1c categories. RESULTS CGM was performed for a median (interquartile range) of 10 (7–12) days/patient. TIR was not different for low and intermediate HbA1c categories (76.8% [68.3–88.2] vs. 76.0% [72.5.0–80.1]), whereas in the low category, TBR was higher and TAR lower (7.7% [2.4–19.1] vs. 0.7% [0.3–6.1] and 8.2% [5.7–17.6] vs. 20.4% [11.6–27.0], respectively; P < 0.05). Patients in the highest HbA1c category had lower TIR (52.7% [40.9–67.3]) and higher TAR (44.1% [27.8–57.0]) than the other HbA1c categories (P < 0.05), but did not have less TBR during the night. All patients had more (0.06 ± 0.06/h vs. 0.03 ± 0.03/h; P = 0.002) and longer (88.0 [45.0–195.5] vs. 53.4 [34.4–82.8] minutes; P < 0.001) TBR episodes during the night than during the day. CONCLUSIONS In this study, a high HbA1c did not reduce the occurrence of nocturnal hypoglycemia, and low HbA1c was not associated with the highest TIR. Optimal personalization of glycemic control requires the use of newer tools, including CGM-derived parameters.

Purpose: To determine whether interrupting sitting with brief bouts of simple resistance activities (SRAs) at different frequencies improves postprandial glucose, insulin and triglycerides in adults with medication-controlled type 2 diabetes (T2D). Methods: Participants [n=23, 10 females, Age: 62±8 y (mean±SD), BMI: 32.7 ± 3.5 kg.m-2] completed a three-armed randomized crossover trial (6-14 day washout): sitting uninterrupted for 7 h (SIT); sitting with 3-minute SRAs (half-squats, calf raises, gluteal contractions, and knee raises) every 30 minutes (SRA3); and, sitting with 6-minute SRAs every 60 minutes (SRA6). Net incremental areas under the curve (iAUCnet) for glucose, insulin, and triglycerides were compared between conditions. Results: Glucose and insulin 7 h iAUCnet were attenuated significantly during SRA6 (glucose 17.0 mmol.h.L-1, 95% CI 12.5, 21.4; insulin 1229 pmol.h.L-1, 95% CI 982, 1538) when compared to SIT (glucose 21.4 mmol.h.L-1, 95% CI 16.9, 25.8; insulin 1411 pmol.h.L-1, 95% CI 1128, 1767; P < 0.05), and compared to SRA3 ( for glucose only; 22.1 mmol.h.L-1, 95% CI 17.7, 26.6; P = 0.01) No significant differences in glucose or insulin iAUCnet were observed comparing SRA3 and SIT. There was no statistically significant effect of condition on triglyceride iAUCnet. Conclusion: In adults with medication-controlled T2D, interrupting prolonged sitting with 6-minute SRAs every 60 minutes reduced postprandial glucose and insulin responses. Other frequencies of interruptions and potential longer-term benefits require examination to clarify clinical relevance.

OBJECTIVE To explore associations between reductions in diabetes distress (DD) and improvements in glycemic outcomes among adults with type 1 diabetes (T1D) in the context of a DD randomized clinical trial. RESEARCH DESIGN AND METHODS Adults with T1D (N = 301) participated in a two-arm trial aimed at reducing DD (DD-focused OnTrack group vs. education-oriented KnowIt group). Mean age was 45.1 years; mean baseline HbA1c was 8.8% (73 mmol/mol). Individuals were assessed at baseline and 9 months later on DD, self-care, HbA1c, and frequency of hypoglycemia. Structural equation models evaluated hypothesized pathways among changes in DD, self-care, and glycemic outcomes in the total sample and by intervention group. RESULTS Reductions in DD were significantly and independently associated with better self-care, including fewer missed insulin boluses, more frequent insulin adjustment, improved problem-solving skills, more blood glucose monitoring, and greater adoption of continuous glucose monitoring (all P < 0.05). In turn, better self-care was linked with better glycemic outcomes, including fewer episodes of hypoglycemia and improved HbA1c over time. Fit indices indicated good fit of the model to the data (confirmatory fit index = 0.94, root mean square error of approximation = 0.05), with stronger and more meaningful associations for OnTrack than for KnowIt. CONCLUSIONS In the context of an intervention to reduce DD for adults with T1D, results indicate that reductions in DD do not affect glycemic outcomes directly but through improvements in self-care behavior. Findings support the importance of integrating disease management with DD interventions to maximize improvements in glycemic outcomes.

OBJECTIVE Disparities in type 1 diabetes related to use of technologies like continuous glucose monitors (CGMs) and utilization of diabetes care are pronounced based on socioeconomic status (SES), race, and ethnicity. However, systematic reports of perspectives from patients in vulnerable communities regarding barriers are limited. RESEARCH DESIGN AND METHODS To better understand barriers, focus groups were conducted in Florida and California with adults ≥18 years old with type 1 diabetes with selection criteria including hospitalization for diabetic ketoacidosis, HbA1c >9%, and/or receiving care at a Federally Qualified Health Center. Sixteen focus groups were conducted in English or Spanish with 86 adults (mean age 42 ± 16.2 years). Transcript themes and pre–focus group demographic survey data were analyzed. In order of frequency, barriers to diabetes technology and endocrinology care included 1) provider level (negative provider encounters), 2) system level (financial coverage), and 3) individual level (preferences). RESULTS Over 50% of participants had not seen an endocrinologist in the past year or were only seen once including during hospital visits. In Florida, there was less technology use overall (38% used CGMs in FL and 63% in CA; 43% used pumps in FL and 69% in CA) and significant differences in pump use by SES (P = 0.02 in FL; P = 0.08 in CA) and race/ethnicity (P = 0.01 in FL; P = 0.80 in CA). In California, there were significant differences in CGM use by race/ethnicity (P = 0.05 in CA; P = 0.56 in FL) and education level (P = 0.02 in CA; P = 0.90 in FL). CONCLUSIONS These findings provide novel insights into the experiences of vulnerable communities and demonstrate the need for multilevel interventions aimed at offsetting disparities in diabetes.

OBJECTIVE: Differences in type 2 diabetes phenotype by age are described, but it is not known whether these differences are seen in a more uniformly defined adult population at a common early stage of care. We sought to characterize age-related clinical and metabolic characteristics of adults with type 2 diabetes on metformin monotherapy, prior to treatment intensification. RESEARCH DESIGN AND METHODS: In the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE), participants were enrolled who had type 2 diabetes duration

OBJECTIVETo evaluate the relation between household food insecurity (HFI) and fear of hypoglycemia among young adults with type 1 and type 2 diabetes and adolescents with type 1 diabetes and their parents.RESEARCH DESIGN AND METHODSWe analyzed cross-sectional data of 1,676 young adults with youth-onset diabetes (84% type 1, 16% type 2) and 568 adolescents (RESULTSAdults with type 1 diabetes experiencing HFI had higher fear of hypoglycemia scores (0.22 units higher for behavior, 0.55 units for worry, 0.40 units for total; all P < 0.0001) than those without HFI. No differences by HFI status were found for adolescents with type 1 diabetes. Parents of adolescents reporting HFI had a 0.18 unit higher worry score than those not reporting HFI (P < 0.05). Adults with type 2 diabetes experiencing HFI had higher fear of hypoglycemia scores (0.19 units higher for behavior, 0.35 units for worry, 0.28 units for total; all P < 0.05) than those in food secure households.CONCLUSIONSScreening for HFI and fear of hypoglycemia among people with diabetes can help providers tailor diabetes education for those who have HFI and therefore fear hypoglycemia.

OBJECTIVE Better preconception metabolic and nutritional health are hypothesized to promote gestational normoglycemia and reduce preterm birth, but evidence supporting improved outcomes with nutritional supplementation starting preconception is limited. RESEARCH DESIGN AND METHODS This double-blind randomized controlled trial recruited from the community 1,729 U.K., Singapore, and New Zealand women aged 18–38 years planning conception. We investigated whether a nutritional formulation containing myo-inositol, probiotics, and multiple micronutrients (intervention), compared with a standard micronutrient supplement (control), taken preconception and throughout pregnancy could improve pregnancy outcomes. The primary outcome was combined fasting, 1-h, and 2-h postload glycemia (28 weeks gestation oral glucose tolerance test). RESULTS Between 2015 and 2017, participants were randomized to control (n = 859) or intervention (n = 870); 585 conceived within 1 year and completed the primary outcome (295 intervention, 290 control). In an intention-to-treat analysis adjusting for site, ethnicity, and preconception glycemia with prespecified P < 0.017 for multiplicity, there were no differences in gestational fasting, 1-h, and 2-h glycemia between groups (β [95% CI] loge mmol/L intervention vs. control −0.004 [−0.018 to 0.011], 0.025 [−0.014 to 0.064], 0.040 [0.004–0.077], respectively). Between the intervention and control groups there were no significant differences in gestational diabetes mellitus (24.8% vs. 22.6%, adjusted risk ratio [aRR] 1.22 [0.92–1.62]), birth weight (adjusted β = 0.05 kg [−0.03 to 0.13]), or gestational age at birth (mean 39.3 vs. 39.2 weeks, adjusted β = 0.20 [−0.06 to 0.46]), but there were fewer preterm births (5.8% vs. 9.2%, aRR 0.43 [0.22–0.82]), adjusting for prespecified covariates. CONCLUSIONS Supplementation with myo-inositol, probiotics, and micronutrients preconception and in pregnancy did not lower gestational glycemia but did reduce preterm birth.

OBJECTIVE We estimated the cost-effectiveness of the Program ACTIVE (Adults Coming Together to Increase Vital Exercise) II community-based exercise (EXER), cognitive behavioral therapy (CBT), and EXER+CBT interventions in adults with type 2 diabetes and depression relative to usual care (UC) and each other. RESEARCH DESIGN AND METHODS Data were integrated into the Michigan Model for Diabetes to estimate cost and health outcomes over a 10-year simulation time horizon from the health care sector and societal perspectives, discounting costs and benefits at 3% annually. Primary outcome was cost per quality-adjusted life-year (QALY) gained. RESULTS From the health care sector perspective, the EXER intervention strategy saved $313 (USD) per patient and produced 0.38 more QALY (cost saving), the CBT intervention strategy cost $596 more and gained 0.29 more QALY ($2,058/QALY), and the EXER+CBT intervention strategy cost $403 more and gained 0.69 more QALY ($585/QALY) compared with UC. Both EXER and EXER+CBT interventions dominated the CBT intervention. Compared with EXER, the EXER+CBT intervention strategy cost $716 more and gained 0.31 more QALY ($2,323/QALY). From the societal perspective, compared with UC, the EXER intervention strategy saved $126 (cost saving), the CBT intervention strategy cost $2,838/QALY, and the EXER+CBT intervention strategy cost $1,167/QALY. Both EXER and EXER+CBT interventions still dominated the CBT intervention. In comparison with EXER, the EXER+CBT intervention strategy cost $3,021/QALY. Results were robust in sensitivity analyses. CONCLUSIONS All three Program ACTIVE II interventions represented a good value for money compared with UC. The EXER+CBT intervention was highly cost-effective or cost saving compared with the CBT or EXER interventions.

OBJECTIVE The optimal method of monitoring glycemia in pregnant women with type 1 diabetes remains controversial. This study aimed to assess the predictive performance of HbA1c, continuous glucose monitoring (CGM) metrics, and alternative biochemical markers of glycemia to predict obstetric and neonatal outcomes. RESEARCH DESIGN AND METHODS One hundred fifty-seven women from the Continuous Glucose Monitoring in Women With Type 1 Diabetes in Pregnancy Trial (CONCEPTT) were included in this prespecified secondary analysis. HbA1c, CGM data, and alternative biochemical markers (glycated CD59, 1,5-anhydroglucitol, fructosamine, glycated albumin) were compared at ∼12, 24, and 34 weeks’ gestation using logistic regression and receiver operating characteristic (ROC) curves to predict pregnancy complications (preeclampsia, preterm delivery, large for gestational age, neonatal hypoglycemia, admission to neonatal intensive care unit). RESULTS HbA1c, CGM metrics, and alternative laboratory markers were all significantly associated with obstetric and neonatal outcomes at 24 weeks’ gestation. More outcomes were associated with CGM metrics during the first trimester and with laboratory markers (area under the ROC curve generally 140 mg/dL [>7.8 mmol/L]) were the most consistently predictive CGM metrics. HbA1c was also a consistent predictor of suboptimal pregnancy outcomes. Some alternative laboratory markers showed promise, but overall, they had lower predictive ability than HbA1c. CONCLUSIONS HbA1c is still an important biomarker for obstetric and neonatal outcomes in type 1 diabetes pregnancy. Alternative biochemical markers of glycemia and other CGM metrics did not substantially increase the prediction of pregnancy outcomes compared with widely available HbA1c and increasingly available CGM metrics (TIR and TAR).

OBJECTIVE Delay discounting and delay aversion are emerging areas for understanding diabetes management; however, few data exist on their relationship with multiple diabetes self-care behaviors and diabetes outcomes. RESEARCH DESIGN AND METHODS This cross-sectional study included 356 adults with type 2 diabetes across three racial/ethnic groups receiving care from two primary care clinics. The primary predictors were delay discounting and delay aversion. Outcomes included self-care behaviors, quality of life (QOL; mental health component score [MCS], physical component score), and A1C. Multiple linear regression models were run to examine the association between predictors and the outcomes, A1C, QOL, and each self-care behavior. RESULTS Higher delay discounting was associated with lower engagement in self-care behaviors for general diet (B = −0.06; 95% CI −0.12; −0.01), specific diet (B = −0.07; 95% CI −0.12; −0.03), and foot care (B = −0.10; 95% CI −0.17; −0.02). Higher delay aversion was associated with lower engagement in self-care behaviors for general diet (B = −0.06; 95% CI −0.10; −0.01), specific diet (B = −0.03; 95% CI −0.07; −0.01), foot care (B = −0.11; 95% CI −0.17; −0.05), and lower MCS (B = −0.38; 95% CI −0.71; −0.06). CONCLUSIONS In a diverse sample of adults with type 2 diabetes, higher delay discounting and higher delay aversion were significantly related to lower engagement in self-care behaviors. High delay aversion was specifically related to lower QOL. These findings offer new knowledge by highlighting the role that delay-related behaviors may have in the performance of self-care behaviors and the impact on QOL. Work is needed to further elucidate these relationships. Specifically, these results highlight the importance of targeting value and decision-making for diabetes self-management.

OBJECTIVE Diabetes is linked to functional decline, but the impact of prediabetes on physical function is unknown. We aimed to examine and compare the impact of prediabetes and diabetes on physical function and disability progression and to explore whether cardiovascular diseases (CVDs) mediate these associations. RESEARCH DESIGN AND METHODS A cohort of 2,013 participants aged ≥60 from the Swedish National Study on Aging and Care in Kungsholmen, an ongoing population-based longitudinal study, was monitored for up to 12 years. Physical function was measured with chair stand (s) and walking speed (m/s) tests, and disability was measured by summing the numbers of impaired basic and instrumental activities of daily living. Diabetes was identified through medical examinations or clinical records, medication use, or glycated hemoglobin (HbA1c) ≥6.5%. Prediabetes was defined as HbA1c ≥5.7–6.4% in participants free of diabetes. CVDs were ascertained through clinical examinations and the National Patient Register. Data were analyzed using mixed-effect models and mediation models. RESULTS At baseline, 650 (32.3%) had prediabetes and 151 had diabetes (7.5%). In multiadjusted mixed-effect models, prediabetes was associated with an increased chair stand time (β 0.33, 95% CI 0.05–0.61), a decreased walking speed (β −0.006, 95% CI −0.010 to −0.002), and an accelerated disability progression (β 0.05, 95% CI 0.01–0.08), even after controlling for the future development of diabetes. Diabetes led to faster functional decline than prediabetes. In mediation analyses, CVDs mediated 7.1%, 7.8%, and 20.9% of the associations between prediabetes and chair stand, walking speed, and disability progression, respectively. CONCLUSIONS Prediabetes, in addition to diabetes, is associated with faster functional decline and disability, independent of the future development of diabetes. This association may be in part mediated by CVDs.

OBJECTIVE The purpose of this study was to use a discrete-choice experiment methodology to understand the relative importance of the attributes of screening tests for type 1 diabetes among parents and pediatricians in the U.S. RESEARCH DESIGN AND METHODS Online surveys presented hypothetical screening test profiles from which respondents chose their preferred test profile. Survey attributes were based on likely screening test options and included the mode of administration, where and when the test was conducted, the type of education and monitoring available to lower the risk of diabetic ketoacidosis (DKA), and whether a treatment was available that would delay onset of insulin dependence. Data were analyzed using random-parameters logit models. RESULTS Parents placed the highest relative importance on monitoring programs that could reduce the risk of DKA to 1%, followed by treatment to delay onset of insulin dependence by 1 or 2 years, and, finally, avoiding a $50 out-of-pocket cost. Pediatricians placed equal importance on monitoring programs that reduced a patient’s risk of DKA to 1% and on avoiding a $50 out-of-pocket cost for the screening test, followed by the option of a treatment to delay the onset of insulin dependence. The mode of administration and location and timing of the screening were much less important to parents and pediatricians. CONCLUSIONS Parents and pediatricians preferred screening tests that were accompanied by education and monitoring plans to reduce the risk of DKA, had available treatment to delay type 1 diabetes, and had lower out-of-pocket costs.

OBJECTIVE To explore the correlates of diabetes-related distress (DD) with psychometrically valid assessments of emotional regulation in individuals with type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS Adults with diabetes (n = 298) were assessed for psychological issues possibly associated with diabetes and were further evaluated with measures of negative emotional experience (ER-Exp) and skill at regulating such experiences (ER-Skill) and measures of DD, perceived psychosocial stress, diabetes literacy, and diabetes self-care. RESULTS ER-Exp was directly related to DD, while ER-Skill was inversely related to DD. Together, these ER variables displayed a medium-size relationship (β = 0.45) with DD. Inclusion of variables related to diabetes self-care and perceived psychosocial stress was associated with only an 18% reduction (i.e., β = 0.45 to β = 0.38) in the strength of this relationship, while the magnitude of relationships between DD and perceived psychosocial stress (β = 0.15) and diabetes self-care (β = −0.09) was relatively small. CONCLUSIONS These data suggest that DD is meaningfully linked with negative emotionality, and skill at regulating such emotions, in adults with diabetes. This relationship appears to be stronger than that between DD and perceived psychological stress or diabetes self-care. If so, DD (and possibly A1C) may be improved in those with diabetes and difficulties with negative emotionality.

OBJECTIVE Across the Diabetes Prevention Program (DPP) follow-up, cumulative diabetes incidence remained lower in the lifestyle compared with the placebo and metformin randomized groups and could not be explained by weight. Collection of self-reported physical activity (PA) (yearly) with cross-sectional objective PA (in follow-up) allowed for examination of PA and its long-term impact on diabetes prevention. RESEARCH DESIGN AND METHODS Yearly self-reported PA and diabetes assessment and oral glucose tolerance test results (fasting glucose semiannually) were collected for 3,232 participants with one accelerometry assessment 11–13 years after randomization (n = 1,793). Mixed models determined PA differences across treatment groups. The association between PA and diabetes incidence was examined using Cox proportional hazards models. RESULTS There was a 6% decrease (Cox proportional hazard ratio 0.94 [95% CI 0.92, 0.96]; P < 0.001) in diabetes incidence per 6 MET-h/week increase in time-dependent PA for the entire cohort over an average of 12 years (controlled for age, sex, baseline PA, and weight). The effect of PA was greater (12% decrease) among participants less active at baseline ( CONCLUSIONS PA was inversely related to incident diabetes in the entire cohort across the study, with cross-sectional accelerometry results supporting these findings. This highlights the importance of PA within lifestyle intervention efforts designed to prevent diabetes and urges health care providers to consider both PA and weight when counseling high-risk patients.

OBJECTIVE Postrandomization biases may influence the estimate of efficacy of supplemental vitamin D in diabetes prevention trials. In the Vitamin D and Type 2 Diabetes (D2d) study, repeated measures of serum 25-hydroxyvitamin D [25(OH)D] level provided an opportunity to test whether intratrial vitamin D exposure affected diabetes risk and whether the effect was modified by trial assignment (vitamin D vs. placebo). RESEARCH DESIGN AND METHODS The D2d study compared the effect of daily supplementation with 100 μg (4,000 units) of vitamin D3 versus placebo on new-onset diabetes in adults with prediabetes. Intratrial vitamin D exposure was calculated as the cumulative rolling mean of annual serum 25(OH)D measurements. Hazard ratios for diabetes among participants who had intratrial 25(OH)D levels of RESULTS There was an interaction of trial assignment with intratrial 25(OH)D level in predicting diabetes risk (interaction P = 0.018). The hazard ratio for diabetes for an increase of 25 nmol/L in intratrial 25(OH)D level was 0.75 (95% CI 0.68–0.82) among those assigned to vitamin D and 0.90 (0.80–1.02) among those assigned to placebo. The hazard ratios for diabetes among participants treated with vitamin D who maintained intratrial 25(OH)D levels of 100–124 and ≥125 nmol/L were 0.48 (0.29–0.80) and 0.29 (0.17–0.50), respectively, compared with those who maintained a level of 50–74 nmol/L. CONCLUSIONS Daily vitamin D supplementation to maintain a serum 25(OH)D level ≥100 nmol/L is a promising approach to reducing the risk of diabetes in adults with prediabetes.

OBJECTIVE The ability of continuous glucose monitoring (CGM) to improve diabetes outcomes depends upon consistent use. To identify factors that facilitate long-term use of CGM, this study tested the hypothesis that youth involvement in the decision to initiate this therapy would influence subsequent CGM use and that CGM self-efficacy and satisfaction mediate this relationship. RESEARCH DESIGN AND METHODS Before initiating CGM, parent-youth dyads (i.e., pairs) from an academic endocrinology clinic completed assessments, including a measure of the child’s involvement in the decision to start CGM. Two months into CGM use, youth completed measures of CGM self-efficacy and satisfaction. Fidelity of CGM use between weeks 5 and 12 was accessed via a cloud-based data repository. Hypotheses were tested with linear mixed-effects models, accounting for patients clustered within provider and repeated measures within patients. RESULTS CGM use in 108 dyads (youth mean age 13.4 ± 2.7 years; 73% White) was positively predicted by baseline parent report of youth involvement in the CGM decision (P < 0.0001), and this relationship was mediated by youth’s perceptions of CGM self-efficacy (P < 0.0001) and hassle (P = 0.014). So, when the youth shared their opinions about CGM with parents and participated in the decision to start, they perceived higher self-efficacy and lower hassle at 2-month follow-up, which predicted more days of use. This pattern held in models adjusting for youth race and sex and family income. CONCLUSIONS To achieve maximum clinical benefit from CGM use, providers should facilitate youth involvement in the decision to initiate the device.

OBJECTIVE Several diabetes clinical practice guidelines suggest that treatment goals may be modified in older adults on the basis of comorbidities, complications, and life expectancy. The long-term benefits of treatment intensification may not outweigh short-term risks for patients with limited life expectancy. Because of the uncertainty of determining life expectancy for individual patients, we sought to develop and validate prognostic indices for mortality in older adults with diabetes. RESEARCH DESIGN AND METHODS We used a prevalence sample of veterans with diabetes who were aged ≥65 years on 1 January 2006 (N = 275,190). Administrative data were queried for potential predictors that included patient demographics, comorbidities, procedure codes, laboratory values and anthropomorphic measurements, medication history, and previous health service utilization. Logistic least absolute shrinkage and selection operator regressions were used to identify variables independently associated with mortality. The resulting odds ratios were then weighted to create prognostic indices of mortality over 5 and 10 years. RESULTS Thirty-seven predictors of mortality were identified: 4 demographic variables, prescriptions for insulin or sulfonylureas or blood pressure medications, 6 biomarkers, previous outpatient and inpatient utilization, and 22 comorbidities/procedures. The prognostic indices showed good discrimination, with C-statistics of 0.74 and 0.76 for 5- and 10-year mortality, respectively. The indices also demonstrated excellent agreement between observed outcome and predictions, with calibration slopes of 1.01 for both 5- and 10-year mortality. CONCLUSIONS Prognostic indices obtained from administrative data can predict 5- and 10-year mortality in older adults with diabetes. Such a tool may enable clinicians and patients to develop individualized treatment goals that balance risks and benefits of treatment intensification.

OBJECTIVE To consider the effects of whole-grain processing, specifically milling, on glycemic control in free-living adults with type 2 diabetes. RESEARCH DESIGN AND METHODS Participants of this crossover trial were randomized to two interventions of 2 weeks, separated by washout. They were advised to replace the grain foods they normally consumed with intervention foods. Intervention foods were nutrient-matched whole-grain products of wheat, oats, and brown rice that differed in their degree of processing. No other lifestyle advice was given. Continuous glucose monitoring systems were worn. Other cardiometabolic risk factors and alkylresorcinols (a biomarker of whole-grain intake) were measured pre- and postintervention. RESULTS Thirty-one adults with type 2 diabetes (63 ± 13 years old, BMI 32.4 ± 7 kg/m2, HbA1c 7.5 ± 3.4% [59 ± 14 mmol/mol]) commenced the trial; 28 (90%) completed both interventions. The increase in alkylresorcinols did not differ between interventions, and there was no difference in reported energy intake. Postprandial responses were 9% (95% CI 3–15) lower following breakfast and 6% (1–10) lower following all meals of less-processed whole grains when compared with finely milled grains. Day-long glycemic variability also was reduced when measured by 24-h SD (−0.16 mmol/L [95% CI −0.25 to −0.06]) and mean amplitude of glycemic excursion (−0.36 [95% CI −0.65 to −0.08]). Mean change in body weight differed by 0.81 kg (95% CI 0.62–1.05) between interventions, increasing during the finely milled intervention and decreasing during the less-processed whole-grain intervention. This was not a mediating factor for the glycemic variables considered. CONCLUSIONS Consuming less-processed whole-grain foods over 2 weeks improved measures of glycemia in free-living adults with type 2 diabetes compared with an equivalent amount of whole-grain foods that were finely milled. Dietary advice should promote the consumption of minimally processed whole grains.

OBJECTIVE Preanalytical processing of blood samples can affect plasma glucose measurement because ongoing glycolysis by cells prior to centrifugation can lower its concentration. In June 2017, ACT Pathology changed the processing of oral glucose tolerance test (OGTT) blood samples for pregnant women from a delayed to an early centrifugation protocol. The effect of this change on the rate of gestational diabetes mellitus (GDM) diagnosis was determined. RESEARCH DESIGN AND METHODS All pregnant women in the Australian Capital Territory (ACT) are recommended for GDM testing with a 75-g OGTT using the World Health Organization diagnostic criteria. From January 2015 to May 2017, OGTT samples were collected into sodium fluoride (NaF) tubes and kept at room temperature until completion of the test (delayed centrifugation). From June 2017 to October 2018, OGTT samples in NaF tubes were centrifuged within 10 min (early centrifugation). RESULTS A total of 7,509 women were tested with the delayed centrifugation protocol and 4,808 with the early centrifugation protocol. The mean glucose concentrations for the fasting, 1-h, and 2-h OGTT samples were, respectively, 0.24 mmol/L (5.4%), 0.34 mmol/L (4.9%), and 0.16 mmol/L (2.3%) higher using the early centrifugation protocol (P < 0.0001 for all), increasing the GDM diagnosis rate from 11.6% (n = 869/7,509) to 20.6% (n = 1,007/4,887). CONCLUSIONS The findings of this study highlight the critical importance of the preanalytical processing protocol of OGTT blood samples used for diagnosing GDM. Delay in centrifuging of blood collected into NaF tubes will result in substantially lower rates of diagnosis than if blood is centrifuged early.

OBJECTIVE To evaluate the efficacy and safety of fast-acting insulin aspart (faster aspart) compared with insulin aspart (IAsp), both with insulin degludec with or without metformin, in adults with type 2 diabetes not optimally controlled with a basal-bolus regimen. RESEARCH DESIGN AND METHODS This multicenter, double-blind, treat-to-target trial randomized participants to faster aspart (n = 546) or IAsp (n = 545). All available information, regardless of treatment discontinuation or use of ancillary treatment, was used for evaluation of effect. RESULTS Noninferiority for the change from baseline in HbA1c 16 weeks after randomization (primary end point) was confirmed for faster aspart versus IAsp (estimated treatment difference [ETD] −0.04% [95% CI −0.11; 0.03]; −0.39 mmol/mol [−1.15; 0.37]; P < 0.001). Faster aspart was superior to IAsp for change from baseline in 1-h postprandial glucose (PPG) increment using a meal test (ETD −0.40 mmol/L [−0.66; −0.14]; −7.23 mg/dL [−11.92; −2.55]; P = 0.001 for superiority). Change from baseline in self-measured 1-h PPG increment for the mean over all meals favored faster aspart (ETD −0.25 mmol/L [−0.42; −0.09]); −4.58 mg/dL [−7.59; −1.57]; P = 0.003). The overall rate of treatment-emergent severe or blood glucose (BG)–confirmed hypoglycemia was statistically significantly lower for faster aspart versus IAsp (estimated treatment ratio 0.81 [95% CI 0.68; 0.97]). CONCLUSIONS In combination with insulin degludec, faster aspart provided effective overall glycemic control, superior PPG control, and a lower rate of severe or BG-confirmed hypoglycemia versus IAsp in adults with type 2 diabetes not optimally controlled with a basal-bolus regimen.

OBJECTIVE We evaluated the effect of optimizing metformin dosing on glycemia and body weight in type 2 diabetes. RESEARCH DESIGN AND METHODS This was a prespecified analysis of 6,823 participants in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) taking metformin as the sole glucose-lowering drug who completed a 4- to 14-week (mean ± SD 7.9 ± 2.4) run-in in which metformin was adjusted to 2,000 mg/day or a maximally tolerated lower dose. Participants had type 2 diabetes for RESULTS Adjusted for duration of run-in, the mean ± SD change in HbA1c was −0.65 ± 0.02% (−7.1 ± 0.2 mmol/mol) when the dose was increased by ≥1,000 mg/day, −0.48 ± 0.02% (−5.2 ± 0.2 mmol/mol) when the dose was unchanged, and −0.23 ± 0.07% (−2.5 ± 0.8 mmol/mol) when the dose was decreased (n = 2,169, 3,548, and 192, respectively). Higher HbA1c at entry predicted greater reduction in HbA1c (P < 0.001) in univariate and multivariate analyses. Weight loss adjusted for duration of run-in averaged 0.91 ± 0.05 kg in participants who increased metformin by ≥1,000 mg/day (n = 1,894). CONCLUSIONS Optimizing metformin to 2,000 mg/day or a maximally tolerated lower dose combined with emphasis on medication adherence and lifestyle can improve glycemia in type 2 diabetes and HbA1c values ≥6.8% (51 mmol/mol). These findings may help guide efforts to optimize metformin therapy among persons with type 2 diabetes and suboptimal glycemic control.

OBJECTIVE Reparixin is an inhibitor of CXCR1/2 chemokine receptor shown to be an effective anti-inflammatory adjuvant in a pilot clinical trial in allotransplant recipients. RESEARCH DESIGN AND METHODS A phase 3, multicenter, randomized, double-blind, parallel-assignment study (NCT01817959) was conducted in recipients of islet allotransplants randomized (2:1) to reparixin or placebo in addition to immunosuppression. Primary outcome was the area under the curve (AUC) for C-peptide during the mixed-meal tolerance test at day 75 ± 5 after the first and day 365 ± 14 after the last transplant. Secondary end points included insulin independence and standard measures of glycemic control. RESULTS The intention-to-treat analysis did not show a significant difference in C-peptide AUC at both day 75 (27 on reparixin vs. 18 on placebo, P = 0.99) and day 365 (24 on reparixin vs. 15 on placebo, P = 0.71). There was no statistically significant difference between treatment groups at any time point for any secondary variable. Analysis of patient subsets showed a trend for a higher percentage of subjects retaining insulin independence for 1 year after a single islet infusion in patients receiving reparixin as compared with patients receiving placebo (26.7% vs. 0%, P = 0.09) when antithymocyte globulin was used as induction immunosuppression. CONCLUSIONS In this first double-blind randomized trial, islet transplantation data obtained with reparixin do not support a role of CXCR1/2 inhibition in preventing islet inflammation-mediated damage.

Objective: We tested whether the concurrence of food intake and elevated concentration of endogenous melatonin, as occurs in late eating, results in impaired glucose control, in particular in carriers of the type 2 diabetes-associated G allele in the melatonin-receptor-1-b gene (MTNR1B). Research Design and Methods: In a Spanish natural late eating population, a randomized, cross-over study design was performed, following an 8-h fast. Each participant (n=845) underwent two evening 2-h 75g oral glucose tolerance tests (OGTT): an early condition scheduled 4 hours prior to habitual bedtime (“early dinner-timing”), and a late condition scheduled 1 hour prior to habitual bedtime (“late dinner-timing”), simulating an early and a late dinner timing, respectively. Differences in postprandial glucose and insulin responses were determined using incremental area under the curve (AUC) calculated by the trapezoidal method between early and late dinner-timing. Results: Melatonin serum levels were 3.5-fold higher in the late vs. early condition, with late dinner-timing resulting in 6.7% lower insulin area-under-the-curve (AUC) and 8.3% higher glucose AUC. In the late condition MTNR1B G-allele carriers had lower glucose tolerance than non-carriers. Genotype differences in glucose tolerance were attributed to reductions in β-cell function (Pint AUCgluc=0.009, Pint CIR=0.022, Pint DI=0.018). Conclusions: Concurrently high endogenous melatonin and carbohydrate intake, as typical for late eating, impair glucose tolerance, especially in MTNR1B G-risk-allele carriers, attributable to insulin secretion defects.

OBJECTIVE Despite that periodical monitoring of cobalamin (vitamin B12) in metformin-treated patients with diabetes is recommended, cobalamin-associated mortality benefits or risks remain unclear. We investigated the association between cobalamin intake and related biomarkers and mortality risk in adults with diabetes using metformin or not. RESEARCH DESIGN AND METHODS This study included 3,277 adults with type 2 diabetes from the National Health and Nutrition Examination Survey (NHANES) and followed up until 31 December 2015. Weighted Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs for mortality risk. RESULTS Among 3,277 participants, 865 all-cause deaths occurred during a median follow-up of 7.02 years. There was no robust relationship between all-cause mortality and serum cobalamin or intake of foods or cobalamin supplements, regardless of metformin treatment (each P ≥ 0.120). The doubling of methylmalonic acid (MMA), a cobalamin-deficiency marker, was significantly associated with higher all-cause (HR 1.31 [95% CI 1.18–1.45], P < 0.001) and cardiac (HR 1.38 [95% CI 1.14–1.67], P = 0.001) mortality. Cobalamin sensitivity was assessed by the combination of binary B12low/high and MMAlow/high (cutoff values: cobalamin 400 pg/mL, MMA 250 nmol/L). Patients with decreased cobalamin sensitivity (MMAhighB12high) had the highest mortality risk. The multivariable-adjusted HRs (95% CIs) of all-cause mortality in MMAlowB12low, MMAlowB12high, MMAhighB12low, and MMAhighB12high groups were 1.00 (reference), 0.98 (0.75–1.28), 1.49 (1.16–1.92), and 1.96 (1.38–2.78), respectively. That association was especially significant in metformin nonusers. CONCLUSIONS Serum and dietary cobalamin were not associated with reduced mortality. Decreased cobalamin sensitivity was significantly associated with all-cause and cardiac mortality, particularly among metformin nonusers.

OBJECTIVE To examine whether characteristics of workplace psychosocial resources are associated with the risk of type 2 diabetes among employees. RESEARCH DESIGN AND METHODS Participants were 49,835 employees (77% women, aged 40–65 years, and diabetes free at baseline) from the Finnish Public Sector cohort study. Characteristics of horizontal (culture of collaboration and support from colleagues) and vertical (leadership quality and organizational procedural justice) psychosocial resources were self-reported. Incident type 2 diabetes (n = 2,148) was ascertained through linkage to electronic health records from national registers. We used latent class modeling to assess the clustering of resource characteristics. Cox proportional hazards models were used to examine the relationship between the identified clusters and risk of type 2 diabetes during 10.9 years of follow-up, adjusting for age, sex, marital status, educational level, type of employment contract, comorbidity, and diagnosed mental disorders. RESULTS We identified four patterns of workplace psychosocial resources: unfavorable, favorable vertical, favorable horizontal, and favorable vertical and horizontal. Compared with unfavorable, favorable vertical (hazard ratio 0.87 [95% CI 0.78; 0.97]), favorable horizontal (0.77 [0.67; 0.88]), and favorable vertical and horizontal (0.77 [0.68; 0.86]) resources were associated with a lower risk of type 2 diabetes, with the strongest associations seen in employees at age ≥55 years (Pinteraction = 0.03). These associations were robust to multivariable adjustments and were not explained by reverse causation. CONCLUSIONS A favorable culture of collaboration, support from colleagues, leadership quality, and organizational procedural justice are associated with a lower risk of employees developing type 2 diabetes than in those without such favorable workplace psychosocial resources.

OBJECTIVE Patients with type 2 diabetes are encouraged to lose weight, but excessive weight loss in older adults may be a marker of poor health and subsequent mortality. We examined weight change during the postintervention period of Look AHEAD, a randomized trial comparing intensive lifestyle intervention (ILI) with diabetes support and education (DSE) (control) in overweight/obese individuals with type 2 diabetes and sought to identify predictors of excessive postintervention weight loss and its association with mortality. RESEARCH DESIGN AND METHODS These secondary analyses compared postintervention weight change (year 8 to final visit; median 16 years) in ILI and DSE in 3,999 Look AHEAD participants. Using empirically derived trajectory categories, we compared four subgroups: weight gainers (n = 307), weight stable (n = 1,561), steady losers (n = 1,731), and steep losers (n = 380), on postintervention mortality, demographic variables, and health status at randomization and year 8. RESULTS Postintervention weight change averaged −3.7 ± 9.5%, with greater weight loss in the DSE than the ILI group. The steep weight loss trajectory subgroup lost on average 17.7 ± 6.6%; 30% of steep losers died during postintervention follow-up versus 10–18% in other trajectories (P < 0001). The following variables distinguished steep losers from weight stable: baseline, older, longer diabetes duration, higher BMI, and greater multimorbidity; intervention, randomization to control group and less weight loss in years 1–8; and year 8, higher prevalence of frailty, multimorbidity, and depressive symptoms and lower use of weight control strategies. CONCLUSIONS Steep weight loss postintervention was associated with increased risk of mortality. Older individuals with longer duration of diabetes and multimorbidity should be monitored for excessive unintentional weight loss.

OBJECTIVE Identifying maturity-onset diabetes of the young (MODY) in pediatric populations close to diabetes diagnosis is difficult. Misdiagnosis and unnecessary insulin treatment are common. We aimed to identify the discriminatory clinical features at diabetes diagnosis of patients with glucokinase (GCK), hepatocyte nuclear factor-1A (HNF1A), and HNF4A MODY in the pediatric population. RESEARCH DESIGN AND METHODS Swedish patients (n = 3,933) aged 1–18 years, diagnosed with diabetes May 2005 to December 2010, were recruited from the national consecutive prospective cohort Better Diabetes Diagnosis. Clinical data, islet autoantibodies (GAD insulinoma antigen-2, zinc transporter 8, and insulin autoantibodies), HLA type, and C-peptide were collected at diagnosis. MODY was identified by sequencing GCK, HNF1A, and HNF4A, through either routine clinical or research testing. RESULTS The minimal prevalence of MODY was 1.2%. Discriminatory factors for MODY at diagnosis included four islet autoantibody negativity (100% vs. 11% not-known MODY; P = 2 × 10−44), HbA1c (7.0% vs. 10.7% [53 vs. 93 mmol/mol]; P = 1 × 10−20), plasma glucose (11.7 vs. 26.7 mmol/L; P = 3 × 10−19), parental diabetes (63% vs. 12%; P = 1 × 10−15), and diabetic ketoacidosis (0% vs. 15%; P = 0.001). Testing 303 autoantibody-negative patients identified 46 patients with MODY (detection rate 15%). Limiting testing to the 73 islet autoantibody-negative patients with HbA1c CONCLUSIONS At diagnosis of pediatric diabetes, absence of all islet autoantibodies and modest hyperglycemia (HbA1c

OBJECTIVE Difficulty achieving preset goals (e.g., ≥5% weight loss, ≥150 min of weekly physical activity) in the yearlong National Diabetes Prevention Program (NDPP) can prompt dropout and diminish benefits. We piloted a more patient-centered NDPP adaptation (NDPP-Flex) that promotes a variety of attainable and individually tailored goals to reduce diabetes risks, along with flexibility to adjust goals each week as needed. RESEARCH DESIGN AND METHODS Retention, physical activity, weight, and glycated hemoglobin (HbA1c) were evaluated among diverse participants with diabetes risks who received our pilot of NDPP-Flex beginning in January and July 2018 (n = 95), with a planned comparison with standard NDPP delivery in preceding cohorts that launched between September 2016 and October 2017 (n = 245). Both the standard NDPP and NDPP-Flex interventions were 1 year in duration and implemented in phases (i.e., nonrandomized). RESULTS Average adjusted retention (e.g., 158.90 ± 15.20 vs. 166.71 ± 9.38 days; P = 0.674), physical activity (157.97 ± 11.91 vs. 175.64 ± 7.54 weekly min; P = 0.231), and weight loss (1.46 ± 0.38% vs. 1.90 ± 0.24%; P = 0.396) were similar between NDPP-Flex versus standard NDPP. However, NDPP-Flex participants had greater HbA1c reduction on average (0.22 ± 0.05% vs. 0.06 ± 0.03%; P = 0.018) and were more likely to have normoglycemia at follow-up (odds ratio 4.62; P = 0.013 [95% CI 1.38–15.50]) than participants in the standard NDPP. CONCLUSIONS An adapted, more patient-centered NDPP that focuses on flexible, self-selected goals may be a promising strategy to improve glycemia even in the absence of substantial weight loss.

OBJECTIVE To determine the longer-term effects of metformin treatment and behavioral weight loss on gut microbiota and short-chain fatty acids (SCFAs). RESEARCH DESIGN AND METHODS We conducted a 3-parallel-arm, randomized trial. We enrolled overweight/obese adults who had been treated for solid tumors but had no ongoing cancer treatment and randomized them (n = 121) to either 1) metformin (up to 2,000 mg), 2) coach-directed behavioral weight loss, or 3) self-directed care (control) for 12 months. We collected stool and serum at baseline (n = 114), 6 months (n = 109), and 12 months (n = 105). From stool, we extracted microbial DNA and conducted amplicon and metagenomic sequencing. We measured SCFAs and other biochemical parameters from fasting serum. RESULTS Of the 121 participants, 79% were female and 46% were Black, and the mean age was 60 years. Only metformin treatment significantly altered microbiota composition. Compared with control, metformin treatment increased amplicon sequence variants for Escherichia (confirmed as Escherichia coli by metagenomic sequencing) and Ruminococcus torques and decreased Intestinibacter bartlettii at both 6 and 12 months and decreased the genus Roseburia, including R. faecis and R. intestinalis, at 12 months. Effects were similar in comparison of the metformin group with the behavioral weight loss group. Metformin versus control also increased butyrate, acetate, and valerate at 6 months (but not at 12 months). Behavioral weight loss versus control did not significantly alter microbiota composition but did increase acetate at 6 months (but not at 12 months). Increases in acetate were associated with decreases in fasting insulin. Additional whole-genome metagenomic sequencing of a subset of the metformin group showed that metformin altered 62 metagenomic functional pathways, including an acetate-producing pathway and three pathways in glucose metabolism. CONCLUSIONS Metformin, but not behavioral weight loss, impacted gut microbiota composition at 6 months and 12 months. Both metformin and behavioral weight loss altered circulating SCFAs at 6 months, including increasing acetate, which correlated with lower fasting insulin. Future research is needed to elucidate whether the gut microboime mediates or modifies metformin’s health effects.

Objetive: Depression is common in people with diabetes, but data from developing countries are scarce. We evaluated the prevalence and risk factors for depressive symptoms in patients with diabetes using data from the International Diabetes Management Practices Study (IDMPS). Research and methods: IDMPS is an ongoing multinational, cross-sectional study investigating quality of care in patients with diabetes in real-world settings. Data from wave 5 (2011), including 21 countries, were analyzed using the 9-item Patient Health Questionnaire (PHQ-9) to evaluate depressive symptoms. Logistic regression analyses were conducted to identify risk factors of depressive symptoms. Results: Of 9,865 patients eligible for analysis, 2,280 had type 1 and 7,585 had type 2 diabetes (treatment: oral glucose-lowering drugs [OGLD] only, n = 4,729; OGLDs plus insulin, n = 1,892; insulin only, n = 964). Depressive symptoms (PHQ-9 score ≥5) were reported in 30.7% of those with type 1 diabetes. In patients with type 2 diabetes, the respective figures were 29.0% for OGLDs-only, 36.6% for OGLDs-plus-insulin, and 46.7% for insulin-only subgroups. Moderate depressive symptoms (PHQ-9 score 10–19) were observed in 8–16% of patients with type 1 or type 2 diabetes. Female sex, complications, and low socioeconomic status were independently associated with depressive symptoms. In type 1 diabetes and in the type 2 diabetes OGLDs-only group, depression was associated with poor glycemic control. Conclusions: Depressive symptoms are common in patients with diabetes from developing countries, calling for routine screening, especially in high-risk groups, to reduce the double burden of diabetes and depression and their negative interaction., Centro de Endocrinología Experimental y Aplicada

OBJECTIVE To simulate the long-term cost-effectiveness of a peer leader (PL)–led diabetes self-management support (DSMS) program following a structured community health worker (CHW)–led diabetes self-management education (DSME) program in reducing risks of complications in people with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS The trial randomized 222 Latino adults with T2D to 1) enhanced usual care (EUC); 2) a CHW-led, 6-month DSME program and 6 months of CHW-delivered monthly telephone outreach (CHW only); or 3) a CHW-led, 6-month DSME program and 12 months of PL-delivered weekly group sessions with telephone outreach to those unable to attend (CHW + PL). Empirical data from the trial and the validated Michigan Model for Diabetes were used to estimate cost and health outcomes over a 20-year time horizon from a health care sector perspective, discounting both costs and benefits at 3% annually. The primary outcome measure was the incremental cost-effectiveness ratio (ICER). RESULTS Over 20 years, the CHW + PL intervention had an ICER of $28,800 and $5,900 per quality-adjusted life-year (QALY) gained compared with the EUC and CHW-only interventions, respectively. The CHW-only intervention had an ICER of $430,600 per QALY gained compared with the EUC intervention. In sensitivity analyses, the results comparing the CHW + PL with EUC and CHW-only interventions were robust to changes in intervention effects and costs. CONCLUSIONS The CHW + PL–led DSME/DSMS intervention improved health and provided good value compared with the EUC intervention. The 6-month CHW-led DSME intervention without further postintervention CHW support was not cost effective in Latino adults with T2D.

Preventive policies to improve diet and physical activity are urgently needed to stem the rising global burden of type 2 diabetes (1). In randomized trials, both high-carbohydrate diets (low in saturated fat and high in fiber), combined with physical activity and caloric restriction, and moderate-fat Mediterranean diets reduced diabetes risk (2). These findings suggest that diets with variable carbohydrate intakes are compatible with diabetes-prevention lifestyles but do not identify the optimal amount and type of dietary carbohydrates. Furthermore, the impact of high carbohydrate intakes in other parts of the world beyond the range studied in Western populations remains unclear. Rice provides ∼20% of the world's calorie intake (3). Of the 10 countries with the largest number of diabetes cases, 6 countries in Asia and South America have rice as the main staple food (4). Rice is predominantly consumed as white rice, a refined grain resulting from a milling process that removes the bran and germ and leaves the starchy endosperm. As a result, white rice is low in fiber, polyphenols, and micronutrients such as magnesium that may benefit glucose metabolism (5–7). White rice also has a high glycemic index (GI) and glycemic load (GL), reflecting high postprandial blood glucose levels (5). In several (8–10) but not all (9–11) prospective cohort studies in Asian countries, higher white rice consumption was associated with a higher risk of type 2 diabetes. Therefore, it is crucial to determine whether white rice consumption contributes to the development of type 2 diabetes, particularly in populations with high intake levels. Bhavadharini et al. (12) evaluated the association between …

OBJECTIVE In September 2016, the U.S. Food and Drug Administration approved the Medtronic 670G “hybrid” closed-loop system. In Auto Mode, this system automatically controls basal insulin delivery based on continuous glucose monitoring data but requires users to enter carbohydrates and blood glucose for boluses. To track real-world experience with this first commercial closed-loop device, we prospectively followed pediatric and adult patients starting the 670G system. RESEARCH DESIGN AND METHODS This was a 1-year prospective observational study of patients with type 1 diabetes starting the 670G system between May 2017 and May 2018 in clinic. RESULTS Of the total of 84 patients who received 670G and consented, 5 never returned for follow-up, with 79 (aged 9–61 years) providing data at 1 week and 3, 6, 9, and/or 12 months after Auto Mode initiation. For the 86% (68 out of 79) with 1-week data, 99% (67 out of 68) successfully started. By 3 months, at least 28% (22 out of 79) had stopped using Auto Mode; at 6 months, 34% (27 out of 79); at 9 months, 35% (28 out of 79); and by 12 months, 33% (26 out of 79). The primary reason for continuing Auto Mode was desire for increased time in range. Reasons for discontinuation included sensor issues in 62% (16 out of 26), problems obtaining supplies in 12% (3 out of 26), hypoglycemia fear in 12% (3 out of 26), multiple daily injection preference in 8% (2 out of 26), and sports in 8% (2 out of 26). At all visits, there was a significant correlation between hemoglobin A1c (HbA1c) and Auto Mode utilization. CONCLUSIONS While Auto Mode utilization correlates with improved glycemic control, a focus on usability and human factors is necessary to ensure use of Auto Mode. Alarms and sensor calibration are a major patient concern, which future technology should alleviate.

OBJECTIVE Depression (major depressive disorder [MDD]) in adults with type 2 diabetes mellitus (T2DM) is associated with worsened diabetes complications, increased health care costs, and early mortality. Program ACTIVE II was a randomized, controlled, multicenter treatment trial designed to test the comparative effectiveness of cognitive behavioral therapy (CBT) and/or community-based exercise (EXER) on diabetes and depression outcomes compared with usual care (UC). RESEARCH DESIGN AND METHODS Using a 2 × 2 factorial randomized controlled trial design, adults with T2DM for ≥1 year who met DSM-IV-TR criteria for MDD were randomized to CBT (10 sessions occurring over 12 weeks; N = 36), EXER (12 weeks of community-based exercise including six sessions with a personal trainer; N = 34), CBT+EXER (concurrent over a 12-week period; N = 34), and UC (N = 36). Primary outcomes were depression remission rate (assessed by psychiatric interviewers blind to assignment) and change in glycemic control (HbA1c). RESULTS The mean age was 56.0 years (SD 10.7). Participants were female (77%), white (71%), and married (52%). After controlling for education and antidepressant use, odds of achieving full MDD remission in the intervention groups were 5.0–6.8 times greater than UC (P < 0.0167). The CBT+EXER group demonstrated improved HbA1c compared with UC. For participants with a baseline HbA1c ≥7.0%, exploratory post hoc subgroup analysis showed that the CBT+EXER group had a 1.1% improvement in HbA1c (P < 0.0001) after controlling for covariates. CONCLUSIONS The Program ACTIVE behavioral treatment interventions demonstrated clinically meaningful improvements in depression outcomes in adults with T2DM and MDD. These community-based interventions are complementary to medical care and extend access to those in rural and urban areas.

OBJECTIVE Type 2 diabetes is related to obesity and altered bone health, and both are affected by gut microbiota. We examined associations of weight loss diet–induced changes in a gut microbiota–related metabolite trimethylamine N-oxide (TMAO), and its precursors (choline and l-carnitine), with changes in bone mineral density (BMD) considering diabetes-related factors. RESEARCH DESIGN AND METHODS In the 2-year Preventing Overweight Using Novel Dietary Strategies trial (POUNDS Lost), 264 overweight and obese participants with measurement of BMD by DXA scan were included in the present analysis. The participants were randomly assigned to one of four diets varying in macronutrient intake. Association analysis was performed in pooled participants and different diet groups. Changes in blood levels of TMAO, choline, and l-carnitine from baseline to 6 months after the dietary intervention were calculated. RESULTS We found that a greater reduction in plasma levels of TMAO from baseline to 6 months was associated with a greater loss in whole-body BMD at 6 months and 2 years (P = 0.03 and P = 0.02). The greater reduction in TMAO was also associated with a greater loss in spine BMD (P = 0.005) at 2 years, independent of body weight changes. The associations were not modified by baseline diabetes status and glycemic levels. Changes in l-carnitine, a precursor of TMAO, showed interactions with dietary fat intake in regard to changes of spine BMD and hip BMD at 6 months (all P < 0.05). Participants with the smallest decrease in l-carnitine showed less bone loss in the low-fat diet group than the high-fat diet group (Pspine = 0.03 and Phip = 0.02). CONCLUSIONS TMAO might protect against BMD reduction during weight loss, independent of diet interventions varying in macronutrient content and baseline diabetes risk factors. Dietary fat may modify the relation between change in plasma l-carnitine level and changes in BMD. Our findings highlight the importance of investigating the relation between TMAO and bone health in patients with diabetes.

OBJECTIVE To determine associations of a Mediterranean diet score (MeDS) with 2-year change in cognitive function by type 2 diabetes and glycemic control status and contrast it against other diet quality scores. RESEARCH DESIGN AND METHODS We used data from the longitudinal Boston Puerto Rican Health Study (n = 913; 42.6% with type 2 diabetes at 2 years). Glycemic control at baseline was categorized as uncontrolled (hemoglobin A1c ≥7% [53 mmol/mol]) versus controlled. Two-year change in glycemic control was defined as stable/improved versus poor/declined. We defined MeDS, Healthy Eating Index, Alternate Healthy Eating Index, and Dietary Approaches to Stop Hypertension scores. Adjusted mixed linear models assessed 2-year change in global cognitive function z score, executive and memory function, and nine individual cognitive tests. RESULTS Higher MeDS, but no other diet quality score, was associated with higher 2-year change in global cognitive function in adults with type 2 diabetes (β ± SE = 0.027 ± 0.011; P = 0.016) but not in those without (P = 0.80). Similar results were noted for Mini-Mental State Examination, word recognition, digit span, and clock drawing tests. Results remained consistent for individuals under glycemic control at baseline (0.062 ± 0.020; P = 0.004) and stable/improved over 2 years (0.053 ± 0.019; P = 0.007), but not for individuals with uncontrolled or poor/declined glycemic control. All diet quality scores were associated with higher 2-year memory function in adults without type 2 diabetes. CONCLUSIONS Both adhering to a Mediterranean diet and effectively managing type 2 diabetes may support optimal cognitive function. Healthy diets, in general, can help improve memory function among adults without type 2 diabetes.

OBJECTIVE This study examines the prevalence of disordered eating behaviors (DEB) and its associations with glycemic control, insulin sensitivity (IS), and psychosocial functioning in a large, diverse cohort of youth and young adults with type 1 or type 2 diabetes. RESEARCH DESIGN AND METHODS In the SEARCH for Diabetes in Youth study, 2,156 youth and young adults with type 1 diabetes (mean ± SD age 17.7 ± 4.3 years; 50.0% female) and 149 youth and young adults with type 2 diabetes (age 21.8 years ± 3.5; 64.4% female) who were receiving insulin therapy completed the Diabetes Eating Problem Survey–Revised (DEPS-R), a self-reported measure for identifying disordered eating. DEB were defined as a DEPS-R score ≥20. Demographic characteristics, clinical measures, and health behaviors of participants with DEB and those without DEB were compared by using t tests. RESULTS DEB were observed in 21.2% of participants with type 1 diabetes and 50.3% of participants with type 2 diabetes. Participants encountered challenges in maintaining a healthy weight while controlling their diabetes. For both types of diabetes, individuals with DEB had a significantly higher BMI z score, lower insulin sensitivity, more depressive symptoms, and poorer quality of life than those without DEB. Diabetic ketoacidosis episodes occurred more frequently in youth with type 1 diabetes with DEB compared to those without DEB. CONCLUSIONS These findings highlight that DEB are prevalent among youth and young adults with type 1 and type 2 diabetes and who are receiving insulin therapy, and DEB are associated with poorer clinical outcomes and psychosocial well-being. Heightened awareness and early interventions are needed to address DEB for this at-risk population, as are longitudinal studies evaluating the course of DEB and diabetes outcomes.

OBJECTIVE Marshallese adults experience high rates of type 2 diabetes. Previous diabetes self-management education (DSME) interventions among Marshallese were unsuccessful. This study compared the extent to which two DSME interventions improved glycemic control, measured on the basis of change in glycated hemoglobin (HbA1c). RESEARCH DESIGN AND METHODS A two-arm randomized controlled trial compared a standard-model DSME (standard DSME) with a culturally adapted family-model DSME (adapted DSME). Marshallese adults with type 2 diabetes (n = 221) received either standard DSME in a community setting (n = 111) or adapted DSME in a home setting (n = 110). Outcome measures were assessed at baseline, immediately after the intervention, and at 6 and 12 months after the intervention and were examined with adjusted linear mixed-effects regression models. RESULTS Participants in the adapted DSME arm showed significantly greater declines in mean HbA1c immediately (−0.61% [95% CI −1.19, −0.03]; P = 0.038) and 12 months (−0.77% [95% CI −1.38, −0.17]; P = 0.013) after the intervention than those in the standard DSME arm. Within the adapted DSME arm, participants had significant reductions in mean HbA1c from baseline to immediately after the intervention (−1.18% [95% CI −1.55, −0.81]), to 6 months (−0.67% [95% CI −1.06, −0.28]), and to 12 months (−0.87% [95% CI −1.28, −0.46]) (P < 0.001 for all). Participants in the standard DSME arm had significant reductions in mean HbA1c from baseline to immediately after the intervention (−0.55% [95% CI −0.93, −0.17]; P = 0.005). CONCLUSIONS Participants receiving the adapted DSME showed significantly greater reductions in mean HbA1c immediately after and 12 months after the intervention than the reductions among those receiving standard DSME. This study adds to the body of research that shows the potential effectiveness of culturally adapted DSME that includes participants’ family members.

OBJECTIVEPoor cognition has been observed in children and adolescents with youth-onset type 1 (T1D) and type 2 diabetes (T2D) compared with control subjects without diabetes. Differences in cognition between youth-onset T1D and T2D, however, are not known. Thus, using data from SEARCH for Diabetes in Youth, a multicenter, observational cohort study, we tested the association between diabetes type and cognitive function in adolescents and young adults with T1D (n = 1,095) or T2D (n = 285).RESEARCH DESIGN AND METHODSCognition was assessed via the National Institutes of Health Toolbox Cognition Battery, and age-corrected composite Fluid Cognition scores were used as the primary outcome. Confounder-adjusted linear regression models were run. Model 1 included diabetes type and clinical site. Model 2 additionally included sex, race/ethnicity, waist-to-height ratio, diabetes duration, depressive symptoms, glycemic control, any hypoglycemic episode in the past year, parental education, and household income. Model 3 additionally included the Picture Vocabulary score, a measure of receptive language and crystallized cognition.RESULTSHaving T2D was significantly associated with lower fluid cognitive scores before adjustment for confounders (model 1; P < 0.001). This association was attenuated to nonsignificance with the addition of a priori confounders (model 2; P = 0.06) and Picture Vocabulary scores (model 3; P = 0.49). Receptive language, waist-to-height ratio, and depressive symptoms remained significant in the final model (P < 0.01 for all, respectively).CONCLUSIONSThese data suggest that while youth with T2D have worse fluid cognition than youth with T1D, these differences are accounted for by differences in crystallized cognition (receptive language), central adiposity, and mental health. These potentially modifiable factors are also independently associated with fluid cognitive health, regardless of diabetes type. Future studies of cognitive health in people with youth-onset diabetes should focus on investigating these significant factors.

OBJECTIVE We investigated the risk of depression and anxiety in people whose spouse did or did not have diabetes. We also examined associations between depression and anxiety and severity of spouse’s diabetes. RESEARCH DESIGN AND METHODS We analyzed prospective self-reported data about diagnosed depression/anxiety and diabetes in cohabiting couples in the national Panel Study of Income Dynamics (PSID) during 1999–2017 (n = 13,500, 128,833 person-years of follow-up, median follow-up 8.1 years). We used Poisson models to estimate incidence and incidence rate ratios (IRRs) of depression/anxiety, according to spouse’s diabetes status overall and by severity of diabetes. RESULTS Age-, sex-, and race-adjusted incidence of depression/anxiety was 8.0/1,000 person-years (95% CI 6.5, 9.6) among those whose spouse had diabetes and 6.5/1,000 person-years (95% CI 6.0, 6.9) among those whose spouse did not have diabetes. Those whose spouse had diabetes had higher risk of depression/anxiety (IRR 1.24 [95% CI 1.01, 1.53]). Those whose spouse had diabetes-related limitations in daily activities (IRR 1.89 [95% CI 1.35, 2.67]) and diabetes combined with other chronic conditions (IRR 2.34 [95% CI 1.78, 3.09]) were more likely to develop depression/anxiety, while those whose spouse had diabetes with no limitations or additional chronic conditions had incidence of depression/anxiety similar to that of subjects whose spouses did not have diabetes. CONCLUSIONS People living with a spouse with diabetes are at higher risk of developing depression/anxiety than people whose spouse does not have diabetes; this risk is driven by the severity of the spouse’s diabetes. Strategies to address the impacts of diabetes on families need to be devised and tested.

OBJECTIVE: Approximately 34 million people in the U.S. have diabetes. With this illness come substantial changes to psychological and physical health. However, type 2 diabetes disproportionately affects non-Hispanic Black compared with non-Hispanic White populations. The purpose of this study was to examine racial differences in psychological, behavioral, and physical health over time among individuals recently diagnosed with type 2 diabetes. RESEARCH DESIGN AND METHODS: Data were collected from a community sample of 193 adults recently diagnosed with type 2 diabetes (44% female; 45% Black). Measures of distress, self-care behaviors, and HbA(1c) were taken at an initial interview (time 1) and 6 months later (time 2). Individuals wore an Actical accelerometer to assess physical activity and participated in three 24-h dietary recall interviews to assess dietary intake within 2 weeks of the initial interview. RESULTS: From time 1 to time 2, Black women showed the highest increase in depressive symptoms. There was a greater increase in regimen and physician distress among White compared with Black participants. White men and Black women reported a decline in medication adherence over time. There were no racial differences in changes in physical activity across 6 months. However, Black individuals had higher overall calorie consumption with greater protein, saturated fat, and cholesterol intake than White individuals. There were no race or sex differences in changes in glycemic stability. CONCLUSIONS: Initial adjustment to a diagnosis of type 2 diabetes differentially influences Black and White men and women in terms of depressive symptoms, diabetes distress, and self-care.

OBJECTIVE Depression is highly frequent in older adults with type 2 diabetes and is associated with cognitive impairment, yet little is known about how various depression dimensions differentially affect cognition. We investigated longitudinal associations of specific depression dimensions with cognitive decline. RESEARCH DESIGN AND METHODS Participants (N = 1,002) were from the Israel Diabetes and Cognitive Decline study, were ≥65 years of age, had type 2 diabetes, and were not experiencing dementia at baseline. Participants underwent a comprehensive neuropsychological battery at baseline and every 18 months thereafter, including domains of episodic memory, attention/working memory, semantic categorization/language, and executive function, and Z-scores of each domain were averaged and further normalized to calculate global cognition. Depression items from the 15-item Geriatric Depression Scale were measured at each visit and subcategorized into five dimensions: dysphoric mood, withdrawal-apathy-vigor (entitled apathy), anxiety, hopelessness, and memory complaint. Random coefficients models examined the association of depression dimensions with baseline and longitudinal cognitive functioning, adjusting for sociodemographics and baseline characteristics, including cardiovascular risk factors, physical activity, and use of diabetes medications. RESULTS In the fully adjusted model at baseline, all dimensions of depression, except for anxiety, were associated with some aspect of cognition (P values from 0.01 to 0.01). CONCLUSIONS Apathy was associated with a faster cognitive decline in executive function. These findings highlight the heterogeneity of depression as a clinical construct rather than as a single entity and point to apathy as a specific risk factor for cognitive decline among older adults with type 2 diabetes.

OBJECTIVE To evaluate associations of oily and nonoily fish consumption and fish oil supplements with incident type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS We included 392,287 middle-aged and older participants (55.0% women) in the UK Biobank who were free of diabetes, major cardiovascular disease, and cancer and had information on habitual intake of major food groups and use of fish oil supplements at baseline (2006–2010). Of these, 163,706 participated in one to five rounds of 24-h dietary recalls during 2009–2012. RESULTS During a median 10.1 years of follow-up, 7,262 incident cases of T2D were identified. Compared with participants who reported never consumption of oily fish, the multivariable-adjusted hazard ratios of T2D were 0.84 (95% CI 0.78–0.91), 0.78 (0.72–0.85), and 0.78 (0.71–0.86) for those who reported CONCLUSIONS Our findings suggest that consumption of oily fish but not nonoily fish was associated with a lower risk of T2D. Use of fish oil supplements, especially constant use over time, was also associated with a lower risk of T2D.

OBJECTIVE During the Diabetes Control and Complications Trial (DCCT), intensive diabetes therapy achieving a mean HbA1c of ∼7% was associated with a threefold increase in the rate of severe hypoglycemia (defined as requiring assistance) compared with conventional diabetes therapy with a mean HbA1c of 9% (61.2 vs. 18.7 per 100 patient-years). After ∼30 years of follow-up, we investigated the rates of severe hypoglycemia in the DCCT/Epidemiology of Diabetes Inverventions and Complications (EDIC) cohort. RESEARCH DESIGN AND METHODS Rates of severe hypoglycemia were reported quarterly during DCCT and annually during EDIC (i.e., patient recall of episodes in the preceding 3 months). Risk factors influencing the rate of severe hypoglycemia over time were investigated. RESULTS One-half of the DCCT/EDIC cohort reported episodes of severe hypoglycemia. During EDIC, rates of severe hypoglycemia fell in the former DCCT intensive treatment group but rose in the former conventional treatment group, resulting in similar rates (36.6 vs. 40.8 episodes per 100 patient-years, respectively) with a relative risk of 1.12 (95% CI 0.91–1.37). A preceding episode of severe hypoglycemia was the most powerful predictor of subsequent episodes. Entry into the DCCT study as an adolescent was associated with an increased risk of severe hypoglycemia, whereas insulin pump use was associated with a lower risk. Severe hypoglycemia rates increased with lower HbA1c similarly among participants in both treatment groups. CONCLUSIONS Rates of severe hypoglycemia have equilibrated over time between the two DCCT/EDIC treatment groups in association with advancing duration of diabetes and similar HbA1c levels. Severe hypoglycemia persists and remains a challenge for patients with type 1 diabetes across their life span.

OBJECTIVE To investigate the effect on pregnancy outcome of integrating a comprehensive management plan for patients with type 1 diabetes (T1D) into the World Health Organization universal maternal care infrastructure. RESEARCH DESIGN AND METHODS A comprehensive preconception-to-pregnancy management plan for women with T1D was implemented in 11 centers from 8 Chinese cities from 2015 to 2017. Sequential eligible pregnant women (n = 133 out of 137 initially enrolled) with T1D and singleton pregnancies attending these management centers formed the prospective cohort. The main outcome was severe adverse pregnancy outcome comprising maternal mortality, neonatal death, congenital malformations, miscarriage in the second trimester, and stillbirth. We compared pregnancy outcomes in this prospective cohort with two control groups with the same inclusion and exclusion criteria: a retrospective cohort (n = 153) of all eligible pregnant women with T1D attending the same management centers from 2012 to 2014 and a comparison cohort (n = 116) of all eligible pregnant women with T1D receiving routine care from 2015 to 2017 in 11 different centers from 7 cities. RESULTS The rate of severe adverse pregnancy outcome was lower in the prospective cohort (6.02%) than in either the retrospective cohort (18.30%; adjusted odds ratio [aOR] 0.31 [95% CI 0.13–0.74]) or the contemporaneous comparison cohort (25.00%; aOR 0.22 [95% CI 0.09–0.52]). CONCLUSIONS The substantial improvements in the prospective cohort are evidence of a potentially clinically important effect of the comprehensive management plan on pregnancy outcomes among Chinese pregnant women with pregestational T1D. This supports the development of similar approaches in other countries.